A major challenge in contemporary health care involves finding solutions to the perplexing problems of human lentivirus infections. Control of HIV-1 and the development of vaccines and antiviral chemotherapies are complicated by the complex pattern of lentivirus gene expression and the propensity for genomic variation common to members of the group. AIDS research is also hindered by the lack of well developed animal models, where vaccines and antiviral drugs can be tested. Equine infectious anemia virus (EIA V) is proving to be a useful system for studying virus mutation during persistent infections, due to the unique periodic nature of these disease. Analyses of the rates and types of EIA V envelope (env) gene mutations occurring during a persistent infection have indicated that they are similar to HIV-1. The research described here is designed to extend the use of EIA V as an animal model for HIV by recovery and analysis of virulent strains of virus, with emphasis on recovery of an infectious molecular clone. We propose several strategies to clone virulent EIA V strains from cell culture as well as directly from infected animals. In contrast to other lentiviruses EIA V is relatively abundant in white blood cells, bone marrow, and other tissues; proviral DNA is present at about 1 copy in 5 to 20 cells facilitating recovery of virus strains that can not be propagated in cell culture. Nucleotide sequences for virulent EIA V strains will be obtained and compared to those of an avirulent cell-adapted virus. Multiple clones will be tested for their ability to replicate upon replication competent clones will tested for the ability to cause disease in Shetland ponies. An infectious molecular clone will be used as a defined starting inoculum for the accurate determination of EIA V mutation rates.